Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35926215.
- Also identified by DOI 10.1021/acs.nanolett.2c00582 and PMC identifier 9479133.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (T<sub>eff</sub>) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/T<sub>eff</sub> cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α<sub>3</sub>β<sub>1</sub> integrin and undergo <i>in situ</i> transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures T<sub>eff</sub> cells via the activatable α<sub>4</sub>β<sub>1</sub> integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The <i>in vivo</i> structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.
Medical subject headings
- Neoplasms
- Tumor Microenvironment